tbuckley/cabot-search huggingface dataset:
Rapid learning of a phonemic discrimination in the first hours of life
Authors: Yan Jing Wu, Xinlin Hou, Cheng Peng, Wenwen Yu, Gary M. Oppenheim, Guillaume Thierry, Dandan Zhang
Journal: Nature Human Behaviour (2022)

Abstract Human neonates can discriminate phonemes, but the neural mechanism underlying this ability is poorly understood. Here we show that the neonatal brain can learn to discriminate natural vowels from backward vowels, a contrast unlikely to have been learnt in the womb. Using functional near-infrared spectroscopy, we examined the neuroplastic changes caused by 5 h of postnatal exposure to random sequences of natural and reversed (backward) vowels (T1), and again 2 h later (T2). Neonates in the experimental group were trained with the same stimuli as those used at T1 and T2. Compared with controls, infants in the experimental group showed shorter haemodynamic response latencies for forward vs backward vowels at T1, maximally over the inferior frontal region. At T2, neural activity differentially increased, maximally over superior temporal regions and the left inferior parietal region. Neonates thus exhibit ultra-fast tuning to natural phonemes in the first hours after birth.
Early patient-reported outcomes are a promising predictive factor of cancer progress and outcome in older patients: The <i>EPROFECY</i> study.
Authors: Carole Helissey, Clémentine Riviere, Charles Parnot, Claire Duverger, Selma Becheriat, Perrine Vuagnat, Antoine Schernberg, Hugo Picchi, Audrey Le Roy, Hélène Vanquaethem, Laurent Brureau
Journal: Journal of Clinical Oncology (2022)

12045 Background: Contrary to commonly-held beliefs, older patients (OPs, aged 70 or more) in oncology are compliant with the use of a telemonitoring digital platform. Such a tool allows the medical team to gain detailed knowledge of the tolerance profile of patients, and help monitor and maintain their quality of life, which is a particularly important goal for older patients. The EPROFECY study assesses the predictive power of the patient health status in the first month of treatment, evaluated with the digital telemonitoring platform Cureety, on survival. Methods: This prospective study was conducted at the Military Hospital Bégin on OPs. Patients were allowed to respond to a symptomatology questionnaire based on CTCAE v.5.0, personalized to their pathology and treatment. An algorithm evaluated the patient status based on reported adverse events: correct (A), compromised (B), to be monitored (C) and critical state (D). For A/B (good health status), the patient received therapeutic advice to help manage each of the reported adverse events. For C/D (poor health status), the patient was invited to call the hospital. To assess the early tolerance of patience to their treatments, we determined the health status in the 1st month after initiation of treatment, which was classified as “Good health” (GH, majority of A/B reports) or “Poor health” (PH, majority of C/D reports). The primary endpoint was to assess if the first-month tolerance is a predictive factor of progression free-survival (PFS). The secondary endpoint was to assess if the first-month tolerance is a predictive factor of overall survival (OS). Results: Sixty-one patients were enrolled between July 1st, 2020 and September 30th, 2021. The median age was 78.0 years (range 70.0 – 99.0), with 81% presenting a metastatic stage, and the most represented cancer being prostate cancer. The median follow-up was 8.2 months. Overall, 2299 ePRO were completed, 89% (n= 2036) corresponding to a "correct" or a "compromised" state and only 11% (n=263) corresponding to a state "to be monitored" or "critical". Based on the first month of questionnaires, 62% of the patients were classified in the GH group, and 38% in the PH group. The PFS ratio at 6 months was 64.6 % in GH vs 23.4 % in PH (HR = 0.1980, 95% CI = 0.04431–0.8845, p = 0.0339). The OS ratio at 6 months was 100% in GH versus 95.5 % in PH (HR: 0.69, 95 % CI = 0.06 – 8.29, p = 0.77). Conclusions: This is the first study that assesses the use of PRO-based tolerance as a predictive factor of treatment response in older individuals. We demonstrated here a significant 80% reduction in the risk of progression in OPs that exhibited a good first-month tolerance. This suggests that e-PRO follow-up might be an effective predictor of response and a tool to treatment plan.
Characterizing the genomic landscape of <i>PIK3CA </i>alterations from 121,221 adult patients with cancer: The next tissue-agnostic target?
Authors: Niamh Coleman, Jason Roszik, Neha K. Reddy, Vivek Subbiah
Journal: Journal of Clinical Oncology (2022)

3088 Background: The PI3K–AKT–mTOR signaling pathway is frequently dysregulated in cancer and small molecule inhibitors targeting various nodes in the pathway have been pursued for decades. Activating mutations in PIK3CA are recognized potent drivers of oncogenesis, though the landscape of PIK3CA fusions and amplifications has yet to be well-defined. The field has been hampered by issues such as resistance and poor tolerance, however several isoform-specific PI3K inhibitors have now received regulatory approval and allosteric pan-mutant and specific mutant selective Inhibitors of PI3Kα are being investigated in early phase clinical trials. Here, we present a comprehensive analysis of PIK3CA alterations in pan-cancer adult malignancies. Methods: We analyzed 136096 samples from 121221 patients available from AACR Project GENIE v.11 database for the prevalence of PIK3CA mutations, fusions and copy number alterations in a range of cancer types. Results: 15712 alterations in PIK3CA were detected in profiled tumor samples (12%), in 14774 of patients profiled (12%), most frequently in endometrial (44% of 4135 cases), anal (35% of 286 cases), breast (35% of 14218 cases), cervical (27% of 761 cases) and colorectal cancer (20% of 3743 cases). PIK3CA alterations identified included 17740 mutations (11%) (including duplicate mutations in patients with multiple samples). 16685 missense mutations were identified (12%);14953 were identified as missense in driver mutation (likely oncogenic)(90% of missense); 1,732 were missense of variants of uncertain significance (VUS) using OncoKB database (11%). Missense mutations most frequently involved codons 545(3347, 20% of missense), codon 1047 (3644, 22%) and codon 542 (1881, 11%). 237 truncating mutations were identified (0.2%), 442 in-frame deletions, 29 in-frame insertion mutations. PIK3CA fusions were observed in 0.06% of tumor samples and were most identified in breast, colorectal, lung, GBM and ovarian cancer (24%, 17%, 13%, 7% and 6% of identified PIK3CA fusions respectively). PIK3CA fusions were most commonly intragenic fusions(36%);common fusion partners included TBL1XR1, FNDC3B and NAALADL2(17%, 7%, 5% of identified PIK3CA fusions, respectively). PIK3CA fusions were identified as VUS, aside from KMT2C-PIK3CA (2%) . PIK3CA amplification high level gain occurred in 0.5% of samples tested(662), deletion occurred in 0.16%(21). Conclusions: Activating PIK3CA mutations occur frequently across cancer types and could be considered for tissue-agnostic drug development. PIK3CA fusion and amplification events are extremely rare. Most PIK3CA missense mutation variants are described as oncogenic, while fusions are described as VUS, which may limit the impact of precision oncology for patients with this alteration. Further functional characterization of PIK3CA variants and basket trial enrollment are warranted.
Breast density changes over time: Frequency, patterns, and practice implications.
Authors: Caitlin Maloney, Shirlene Paul, Jordan Lieberenz, Mia Alyce Levy, Lisa Stempel, Rosalinda Alvarado
Journal: Journal of Clinical Oncology (2022)

e18772 Background: Dense breast tissue is known to obscure malignancy on mammography and is considered an independent risk factor for breast cancer. Because of its clinical significance, breast density has been incorporated into cancer risk assessment tools, supplemental screening recommendations, and patient notification laws. Changes in density—whether due to intrinsic changes in breast tissue over time or to inter-radiologist variability in interpreting mammographic results—can therefore have significant implications for patients. The purpose of this study was to quantify longitudinal patterns of breast density change. Methods: This retrospective cohort study tracked breast density changes among 37,156 patients who received multiple mammograms at a large academic medical center between October 1, 2015 and June 29, 2021. Breast Imaging-Reporting and Data System (BI-RADS) density categories A (least dense) through D (most dense), visually determined by radiologists at the time of screening, were abstracted from electronic medical records and dichotomized into one of two density statuses: non-dense (categories A and B) and dense (categories C and D). A sequence analysis of longitudinal changes between the two density statuses was performed using SQL. Results: The majority (91.3%, n = 33,920) of patients maintained the same density status (dense or non-dense) throughout the six-year study period, while 8.7% of participants (n = 3,236) experienced between one and six density status changes. Among patients who experienced any density status change, the vast majority (96.7%, n = 3,131) moved exclusively between BI-RADS categories B and C, the intermediate density categories (Table). Frequency of density status change was positively correlated with average number of mammograms performed per patient. Conclusions: Although most patients maintain a consistent breast density status, some will experience multiple status changes even over this relatively short timeframe (&lt; 6 years), with more frequent changes being associated with more frequent mammograms. The overwhelming majority of patients whose density status changed moved exclusively between BI-RADS categories B and C, suggesting a role for inter-radiologist variability in visual assessments of intermediate-density tissue. These findings have implications for how density status changes are incorporated into patient education, risk assessment, and supplemental screening recommendations.[Table: see text]
Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial
Authors: Chris C. Parker, Nicholas D. James, Christopher D. Brawley, Noel W. Clarke, Adnan Ali, Claire L. Amos, Gerhardt Attard, Simon Chowdhury, Adrian Cook, William Cross, David P. Dearnaley, Hassan Douis, Duncan C. Gilbert, Clare Gilson, Silke Gillessen, Alex Hoyle, Rob J. Jones, Ruth E. Langley, Zafar I. Malik, Malcolm D. Mason, David Matheson, Robin Millman, Mary Rauchenberger, Hannah Rush, J Martin Russell, Hannah Sweeney, Amit Bahl, Alison Birtle, Lisa Capaldi, Omar Din, Daniel Ford, Joanna Gale, Ann Henry, Peter Hoskin, Mohammed Kagzi, Anna Lydon, Joe M. O’Sullivan, Sangeeta A. Paisey, Omi Parikh, Delia Pudney, Vijay Ramani, Peter Robson, Narayanan Nair Srihari, Jacob Tanguay, Mahesh K. B. Parmar, Matthew R. Sydes
Journal: PLoS Medicine (2022)

Background STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). Methods and findings Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p &lt; 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p &lt; 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. Conclusions Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. Trial registration ClinicalTrials.gov NCT00268476 , ISRCTN.com ISRCTN78818544 .
Prognostic value of hematologic parameters in patients with muscle invasive bladder cancer.
Authors: Vatsala Katiyar, Jasdeep Sidhu, Quan Do, Xiaoyong Wu, Shesh Rai, Talha Aijaz, Anosha Tariq, Vikas Singh
Journal: Journal of Clinical Oncology (2022)

e16502 Background: Muscle invasive bladder cancers (MIBC) tend to have an increased risk of progression and recurrence despite optimal management. Since various blood cells affect tumor microenvironments, modulate tumor growth and treatment responses, we examined the impact of Platelet/Lymphocyte ratio (PLR) and systemic inflammation response index [(SIRI) = N×M/L), N- Neutrophil, M-monocyte, and L-Lymphocyte] at diagnosis of MIBC patients on overall prognosis. Methods: We performed a retrospective analysis of all muscle invasive bladder cancer patients treated at our institute from January 2015 to December 2020. Patients with Stage I and IV disease were excluded. Descriptive statistics were obtained for entire cohort. The optimal cutoff points for PLR and SIRI were accessed by the receiver operating characteristic curve (ROC) based on overall survival (OS) and Progression free survival (PFS). Kaplan-Meier curve was used to compare the OS and the PFS between the groups. Univariate and multivariate Cox regression analyses were used to evaluate the impact of PLR and SIRI on the OS. Results: In our cohort of 112 patients, median age at diagnosis was 65 years (95% CI: 62-68). Patients were predominantly males (74.1%), Caucasians (88.3%), smokers (71.4%), and 59.8% had a BMI above 24.9. The median duration of follow up was 18.7 months (mo). The median OS was 28.5 mo (95% CI: 19.8-55.4) and median PFS was 16.7 mo (95% CI: 11.7-30.0). 50 patients (44.6%) were stage II and 62 patients (55.4%) were Stage III. 34 patients (30.4%) received chemotherapy in neoadjuvant or adjuvant setting, 6 patients (5.4%) received radiotherapy, and majority of patients (total 75; 67.0%) were treated with surgical intervention. The optimal cutoff points on OS for PLR and SIRI were 304.04 and 1.83 respectively. On univariate analysis, SIRI did not affect OS (HR: 1.26, 95% CI: 0.73-2.19, p = 0.406). Patients with high PLR had worse OS on both univariate (HR: 1.003, 95% CI: 1.001-1.005, p = 0.003) and multivariate (HR: 1.002, 95% CI: 1.000-1.004, p = 0.028) analyses. Nodal staging, radiation treatment, and baseline hemoglobin level were other statistically significant factors associated with OS. Conclusions: Although the standard TNM staging system is helpful in predicting tumor behavior, there is marked heterogeneity in responses to treatment for MIBC. Our study suggests that PLR at diagnosis can be a novel prognostic marker for patients with MIBC.
Applicability of a web app for lung cancer risk calculation and personalized recommendations for screening in Mexico.
Authors: Jose Felipe Muñoz Lozano, Victor Oyervides, Carlos Eduardo Salazar-Mejía, Omar A. Zayas, Oscar Vidal-Gutiérrez, Rafael Pineiro-Retif, Diana Cristina Pérez-Ibave, Ricardo Andres Gomez, Brenda Garza, Larisa Renteria
Journal: Journal of Clinical Oncology (2022)

1548 Background: Lung cancer screening continues to be an area of great opportunity in public health, especially in developing countries. In Mexico, about 10,000 new cases of lung cancer are detected annually, of which less than 5% are diagnosed in early stages. There are no national programs for timely detection of lung cancer in our country, so it is essential to seek accessible measures to prioritize resources for high-risk people. Methods: We developed a web app that consisted of a short survey to stratify patients according to their risk of lung cancer (https://cuccuanl.com/tamiz_pulmon/). The questions were based on Nelson's criteria to categorize high-risk subjects who are deemed candidates for screening. The program contained automated logic programmed using JavaScript to guide people to the low or high-risk page if they met standard risk criteria in those age 50 and older. The high-risk page alerted people of their risk, displaying general information about lung cancer as well as contact information to make an appointment at our cancer center. An appointment could be also scheduled within the app if the person so wished. The web app was launched and distributed through social media. Results: After a period of 2 months, 939 people completed the survey. The median age of the responders was 40 years, and 61% were men. Of the total, 185 participants were 50 years of age or older. 268 people (29% of the total) were sent to the high-risk page, including persons under 50 years of age with symptoms highly suggestive of lung cancer. According to their smoking status, 80% of the subjects reported active smoking, while 9% reported heavy smoking, considered as more than 20 pack-years. Among all the people evaluated, 44 high-risk subjects scheduled a specialized medical appointment within the web app. Conclusions: This pilot study showed a high response of Mexican population seeking lung cancer risk evaluation, especially among the persons who smoke regularly. The use of web apps can result in mass diffusion which will help reach people with less medical access, a common scenario in many developing countries. Further analysis should be made to measure the real impact on lung cancer diagnosis and oncological outcomes. Our study shows how effective social media is as a means of diffusion on health topics. [Table: see text][Table: see text]
Profiling of clinically relevant subgroups of asymptomatic or mild-symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients using PSA and testosterone levels and deep learning.
Authors: Juan Manuel Dominguez Correa, Pablo Gomez del Campo, Carlos Maria Galmarini
Journal: Journal of Clinical Oncology (2022)

e17032 Background: The optimal time to begin therapy in mCRPC patients who have either no, or minimal symptoms is not defined yet. Estimating prognosis of these patients can avoid undertreatment or overtreatment and guide the follow-up intensity. This study has investigated the ability of a deep learning framework (DLF) to identify asymptomatic or mildly symptomatic mCRPC patients with high risk of disease progression and mortality using PSA and testosterone levels. Methods: Data from the control arm of the NCT00554229 trial was obtained from www.projectdatasphere.org . These mCRPC patients were treated with placebo alone. The dataset consisted of more than 150 clinical variables. We generated synthetic fingerprints (SF) for each patient through the integration of PSA values collected at baseline and during the first 90 days of follow-up and testosterone levels at baseline. These SF were then input into a DLF to identify subgroup of patients based on their similarities. The resultant subgroups were correlated with progression-free survival (PFS) and overall survival (OS). Feature contribution analysis identified the significant predictive clinical variables in each subgroup. Results: After discarding missing data, 189 patients were eligible for this exploratory study. Median PFS and OS for the total population were 8.7 months and 24.5 months, respectively. DLF identified two different subpopulations, SPA (n = 89) and SPB (n = 100), with significantly different survival outcome. Patients in SPA had a lower risk of progression (median PFS 12.2 months vs. 7.2 months; hazard ratio 0.54, 95% CI 0.41-0.71; p &lt; .0001) and death (median OS not reached vs. 20.3 months; hazard ratio 0.33, 95% CI 0.21-0.52; p &lt; .0001) compared to patients in SPB. SPA signature was significantly correlated to leuprolide treatment. These patients also had higher levels of haemoglobin, red blood cells, haematocrit, total bilirubin, Ca, phosphate, and K. Instead, SPB signature was significantly correlated with presence of &gt; 3 bone metastasis, lack of energy or forced time to bed in the FACT-P and moderate problems in selfcare in the EQ-5D, and treatment with goserelin, tamsulosin, opioids and contact laxatives. In addition, these patients had higher levels of platelets, basophils, monocytes, ALP, AST, LDH, PSA, free PSA, Mg, Na, and specific gravity. Conclusions: DLF identifies mCRPC subtypes that correlate with higher risk of progression and death according to PSA and testosterone levels. Model predictions also suggest complex interactions among many clinical features that might be important modulators of key clinical traits and outcome. Further work is required to validate this approach to anticipate the clinical course of asymptomatic or mildly symptomatic mCRPC patients and help to better decide when to start appropriate therapy.